Half esters are highly versatile building blocks in chemical synthesis, where they provide useful intermediaries to a wide variety of end products. Half esters themselves may be conveniently produced by the selective monohydrolysis of symmetric diesters. Since many symmetric diesters may be readily prepared from inexpensive sources or are commercially available in a variety of grades at commodity prices, synthetic routes based on half ester intermediates provide the additional advantages of economy and versatility.
Saponification or alkaline hydrolysis are both established methods for producing half esters from diesters. However, the application of these approaches to the formation of half esters from symmetric diesters is complicated by the difficulty in chemically distinguishing between the two identical functional groups in the starting diester. Consequently, this approach typically results in a complex mixture of dicarboxylic acids, monocarboxylic acids, and the starting diester. Aside from the obvious yield loss attendant to the formation of dicarboxylic acids and other reaction byproducts, the target half ester is difficult to separate from these reaction byproducts, due to their chemical similarity. Indeed, until recently, the only effective method reported in the literature for the synthesis of half esters from symmetrical diesters involved the use of enzymes. However, such a synthetic route is undesirable in that, among other things, it provides no basis for predictions of reactivity.
More recently, a new synthetic route has been disclosed for the production of half esters from symmetric diesters. This route, which involves the selective hydrolysis and subsequent acidification of the diester, affords the half ester in relatively high yields in a solution that is relatively free of byproducts (see S. Niwayama, “Highly Efficient Selective Monohydrolysis of Symmetric Diesters”, J. Org. Chem. 2000, p 5834). This approach is summarized in SCHEME 1 below:
